A quantitative description of the role of gelation in the pathophysiology of sickle cell disease is being formulated to aid in the in the development of agents that can be used in the treatment of patients. A new laser photolysis technique has been developed to assess the quantitative significance of the delay time of hemoglobin S gelation to the pathophysiology. The saturation at which polymers first form in individual sickle erythrocytes upon reoxygenation. The results indicate that at physiological saturations with oxygen, gelation takes place in the large majority of cells at equilibrium, but is prevented from occuring in vivo because the delay times are sufficiently long that most cells return to the lungs and are reoxygenated before polymerization has begun. These techniques are being extended to measure the delay time as a function of saturation on physiological times scales over a wide range of hemoglobin S concentrations and saturations. With these data it will be possible to provide a more accurate description of gelation in vivo. The measurement of the delay time on single cells in these experiments can also be used as a very sensitive method to assess the potential efficacy of agents that are potential drugs for the treatment of sickle cell disease. The measurement of the distribution of delay times at zero saturation will be automated to permit examination of a large number of agents, to compare intracellular gelation and clinical severity in patients, and to follow changes in intracellular gelation in patients on various therapeutic protocols.